US2018344690A1PendingUtilityA1

Methods and Formulation for Enhancing Response to Radiotherapy

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Assignee: UNIV LELAND STANFORD JUNIORPriority: Jun 2, 2017Filed: Jun 4, 2018Published: Dec 6, 2018
Est. expiryJun 2, 2037(~10.9 yrs left)· nominal 20-yr term from priority
Inventors:John Martin BrownLawrence RechtSeema NagpalReena Thomas
A61P 43/00A61K 9/0019A61K 31/395
37
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Claims

Abstract

Methods of treatment and pharmaceutical formulation configured to improve the cure rate of patients with solid tumors when treated with radiotherapy are provided. The methods and treatments use an inhibitor of the CXCL12/CXCR4 pathway. The inhibitors prevent the formation of new blood vessels into a tumor that is being treated with radiotherapy. The inhibitor may be continuously infused intravenously towards the end of radiotherapy and continuing thereafter.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of enhancing a response to radiotherapy in tumors comprising:
 administering a therapeutically effective amount of a CXCL12/CXCR4 inhibitor to a patient undergoing radiotherapy for a tumor.   
     
     
         2 . The method of  claim 1 , wherein the CXCL12/CXCR4 inhibitor is Plerixafor. 
     
     
         3 . The method of  claim 2 , wherein the Plerixafor is administered at a dose of at least 200 μg/kg/d. 
     
     
         4 . The method of  claim 2 , wherein the Plerixafor is administered at a dose of at least 400 μg/kg/d. 
     
     
         5 . The method of  claim 1 , wherein the CXCL12/CXCR4 inhibitor is infused intravenously. 
     
     
         6 . The method of  claim 1 , wherein the administering step begins at a point prior to a peak of SDF-1 expression. 
     
     
         7 . The method of  claim 1 , wherein the tumor is a solid tumor. 
     
     
         8 . The method of  claim 1 , wherein the tumor is a glioblastoma. 
     
     
         9 . The method of  claim 1 , wherein the CXCL12/CXCR4 inhibitor prevents the formation of new blood vessels in the tumor. 
     
     
         10 . The method of  claim 1 , wherein the CXCL12/CXCR4 inhibitor prevents TAM accumulation in the tumor. 
     
     
         11 . A pharmaceutical formulation for the prevention and treatment of the recurrence of tumors comprising a therapeutically effective amount of a CXCL12/CXCR4 inhibitor to a patient undergoing radiotherapy for a tumor. 
     
     
         12 . The pharmaceutical formulation of  claim 11 , wherein the CXCL12/CXCR4 inhibitor is Plerixafor. 
     
     
         13 . The pharmaceutical formulation of  claim 12 , wherein the therapeutically effective amount is at least 200 μg/kg/d. 
     
     
         14 . The pharmaceutical formulation of  claim 12 , wherein the therapeutically effective amount is at least 400 μg/kg/d. 
     
     
         15 . The pharmaceutical formulation of  claim 11 , wherein the pharmaceutical formulation is infused intravenously. 
     
     
         16 . The pharmaceutical formulation of  claim 11 , wherein the pharmaceutical formulation is administered at a point prior to a peak of SDF-1 expression. 
     
     
         17 . The pharmaceutical formulation of  claim 11 , wherein the tumor is a solid tumor. 
     
     
         18 . The pharmaceutical formulation of  claim 11 , wherein the tumor is a glioblastoma. 
     
     
         19 . The pharmaceutical formulation of  claim 11 , wherein the CXCL12/CXCR4 inhibitor prevents the formation of new blood vessels in the tumor. 
     
     
         20 . The pharmaceutical formulation of  claim 11 , wherein the CXCL12/CXCR4 inhibitor prevents TAM accumulation in the tumor.

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